Methods and compositions for the treatment of ischemic injury to tissue using therapeutic hypothermia

Abstract

Disclosed are compositions and methods for inducing therapeutic hypothermia in a subject.

What is claimed is: 
     
       1. A method of treating ischemic brain injury caused by cardiac arrest in a subject comprising administering to the subject a therapeutically effective amount of an A 1  adenosine receptor (A 1 AR) agonist and an A 1 AR antagonist, wherein the A 1 AR agonist is capadenoson, or a combination of capadenoson with N 6 -cyclohexyladenosine (CHA), and the A 1 AR antagonist is 8-p-sulfophenyltheophylline (8-SPT), wherein the A 1 AR agonist crosses the blood brain barrier and wherein the A 1 AR antagonist does not cross the blood-brain barrier, and wherein treating ischemic brain injury involves alleviating shivering in the subject. 
     
     
       2. The method of  claim 1 , further comprising inducing therapeutic hypothermia in the subject. 
     
     
       3. The method of  claim 2 , further comprising maintaining hypothermia in the subject. 
     
     
       4. The method of  claim 3 , wherein maintaining hypothermia in the patient comprises repeating the administration of the A 1 AR agonist and the A 1 AR antagonist. 
     
     
       5. The method of  claim 1 , wherein the A 1 AR agonist and the A 1 AR antagonist are co-administered. 
     
     
       6. The method of  claim 1 , wherein the A 1 AR antagonist is titrated to minimize side effects of the agonist. 
     
     
       7. A method of controlling core body temperature in a subject comprising administering to the subject a therapeutically effective amount of an A 1 AR agonist and an A 1 AR antagonist, wherein the A 1 AR agonist is capadenoson or a combination of capadenoson with CHA, and the A 1 AR antagonist is 8-SPT, wherein the A 1 AR agonist crosses the blood brain barrier and wherein the A 1 AR antagonist does not cross the blood-brain barrier, wherein the A1AR agonist alleviates shivering. 
     
     
       8. The method of  claim 7 , wherein the subject had an ischemic brain injury.